A case of thrombosed aneurysm of the vein of Galen associated with superior sagittal sinus thrombosis

A case of thrombosed aneurysm of the vein of Galen associated with superior sagittal sinus thrombosis is reported. Clinical course was characterized by multiple intraparenchimatous hemorrhages and hydrocephalus. NMR showed dural sinuses thrombosis better than CT even though cerebral angiography was more effective for the diagnosis. Intracranial hypertension due to hydrocephalus was relieved with a ventriculoperitoneal shunt. The authors suggest that the abnormal hemodynamic patterns due to the drainage of the malformation into the vein of Galen and dural sinuses led to venous occlusion and multiple intracranial hemorrhages.     

Testing for IgG class antibodies in celiac disease patients with selective IgA deficiency. A comparison of the diagnostic accuracy of 9 IgG anti-tissue transglutaminase, 1 IgG anti-gliadin and 1 IgG anti-deaminated gliadin peptide antibody assays

BACKGROUND: To evaluate the diagnostic characteristics of commercially available IgG anti-tTG assays in selective IgA deficiency (SIgAD), we tested different IgG anti-tTG methods and compared the results with those obtained from two other tests: one for IgG anti-gliadin (AGA) and one for IgG to deaminated gliadin peptides (DGP). METHODS: 20 CD patients with SIgAD and 113 controls (9 patients with SIgAD without CD; 54 patients with chronic liver disease; 50 healthy subjects) were tested with 9 IgG anti-tTG assays (2 of which are enriched with gliadin peptides), one IgG AGA assay and one IgG anti-DGP assay. RESULTS: Using optimal cutoffs as determined by ROC curves, the sensitivity of IgG anti-tTG methods ranged from 75% (1 kit) to 95% (7 kits) and the specificity from 94% (1 kit) to 100% (5 kits). Sensitivity and specificity were 40% and 87% for IgG AGA, and 80% and 98% for IgG anti-DGP, respectively. CONCLUSIONS: All IgG anti-tTG methods evaluated are reliable serologic assays for the diagnosis of CD in patients with SIgAD and perform better than the gliadin-based assays used in this study. The tests containing both tTG and gliadinic peptides are burdened by a lower specificity than the anti-tTG assays.     

Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management

A condition defined as nonalcoholic fatty liver disease (NAFLD) is frequently found in humans. Deemed as a benign condition until recently, more emphasis is now put on the potential harmful evolution of the inflammatory form, that is, nonalcoholic steatohepatitis (NASH), toward end-stage liver disease. This review highlights the major morphologic and pathophysiological features of NASH. The link between experimental biochemical findings in animal models and clinical and therapeutic approaches in humans is discussed. Once all the other causes of persistent elevation of serum transaminase levels have been excluded, the diagnosis of NASH can be only confirmed by liver histology. Other noninvasive diagnostic tools, however, are being investigated to assess specific subcellular functions and to allow the follow-up of patients at higher risk for major liver dysfunction. A better understanding of various pathogenic aspects of NASH will help in identifying potential therapeutic approaches in these patients.     

Are the ACR 2010 diagnostic criteria for fibromyalgia better than the 1990 criteria?

Fibromyalgia (FM) is difficult to diagnose and manage chronic pain condition whose symptoms have no clear pathophysiological cause, although it is thought that patient hypersensitivity to a range of stimuli may give rise to mechanical hyperalgesia as a result of altered central nociceptive processing. The 1990 American College of Rheumatology (ACR) classification criteria, which have been widely used in clinical practice, require the existence of chronic widespread pain (CWP) for > 3 months, and the presence of at least 11 out of 18 specified tender points upon digital palpation, although this latter criterion has long been criticised. The newer 2010 ACR diagnostic criteria state that FM can be defined as CWP associated with somatic symptoms, and recommend the use of a widespread pain index and a scale to rate symptom severity. A modified version of the 2010 criteria removed the physician assessment of the extent of somatic symptoms and replaced it by a summary score of three self-reported symptoms, thus making it easier to use while maintaining its sensitivity. This review discusses the advantages and limitations of all of these criteria.     

Esomeprazole-induced central fever with severe myalgia

OBJECTIVE: To report a case of central fever associated with severe myalgia following esomeprazole. CASE SUMMARY: A 64-year-old man presented with intense cephalalgia; severe, diffuse myalgia; and fever (>40 degrees C) after esomeprazole initiation for treatment of gastritis. Five hours after ingestion of the first esomeprazole pill (40 mg), the patient developed fever associated with cephalalgia and myalgia. This condition lasted about 40 hours and disappeared spontaneously. Symptoms partially responded to acetaminophen. Four days later, the patient received a second dose of esomeprazole 40 mg. Subsequently, 4 hours later, fever (>40 degrees C), headache, and difficulty in the movement of all parts of the body recurred. Neurologic examination was negative except for a minor state of disorientation. All reflexes were normal or slightly decreased. No skin lesions or breathing difficulty was noted. Routine blood tests were normal. Again, symptoms resolved spontaneously about 40 hours later. DISCUSSION: The temporal connection between esomeprazole intake and the onset of fever suggests a probable causal link, as confirmed by the Naranjo probability scale. However, the pathogenic mechanism remains unclear. Considering that esomeprazole is able to cross the blood-brain barrier, its peak serum concentration is reached 90-180 minutes after oral administration, and its serum half-life is approximately 2 hours, we assume that the appearance of fever with accompanying neurologic and muscular symptoms might result from the drug interference with the hypothalamic regulatory center of body temperature. CONCLUSIONS: Hyperpyrexia of central origin associated with intense cephalalgia and myalgia may occur as an adverse effect of esomeprazole therapy.     

Pathophysiology of ultrafiltration in peritoneal dialysis

Pathophysiology of peritoneal ultrafiltration is analyzed in the present study. Peritoneal equilibration test is the easiest procedure to study in detail the possible causes of failure to control the ultrafiltration rate in patients undergoing peritoneal dialysis. Membrane failure, reduction in peritoneal blood flow, excessive lymphatic reabsorption catheter malposition, and fluid sequestration are the most common causes of ultrafiltration loss. Pharmacologic manipulation of peritoneal membrane, correction of mechanical inconvenients, reduction in peritonitis rate and in the level of immunostimulation of the mesothelial macrophages, together with a careful policy in terms of glucose concentration in the dialysate and dwell times may contribute not only to treat different forms of ultrafiltration loss but also to prevent their incidence.     

Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha?

Elevated plasminogen activator inhibitor-1 (PAI-1) plasma levels, responsible for reduced fibrinolysis, are associated with animal and human obesity and with increased cardiovascular disease. The expression of PAI-1 has been found recently in animal and human adipose tissue. Factors and mechanisms regulating such an expression remain to be elucidated. In omental and/or subcutaneous biopsies from obese non-diabetic patients, incubated in Medium 199, we have confirmed that human adipose tissue expresses PAI-1 protein and mRNA; furthermore we have demonstrated that such an expression is clearly evident also in collagenase isolated human adipocytes and that it is stimulated by incubation itself and enhanced by exogenous human tumor necrosis factor-alpha (h-TNF-alpha). Since human adipose tissue produces TNF-alpha, to further characterize the relationship of PAI-1 to TNF-alpha, human fat biopsies were also incubated with Pentoxifylline (PTX) or Genistein, both known to inhibit endogenous TNF-alpha through different mechanisms. PTX caused a dose-dependent decrease of basal PAI-1 protein release, reaching 80% maximal inhibitory effect at 10(-3)M, the same inhibitory effect caused by Genistein at 100 microg/ml. This was associated to a marked inhibition of PAI-1 mRNA and of endogenous TNF-alpha production. Furthermore, when human fat biopsies were incubated in the presence of polyclonal rabbit neutralizing anti-human TNF-alpha antibody (at a concentration able to inhibit 100 UI/ml human TNF-alpha activity), a modest but significant decrease of the incubation induced expression of PAI-1 mRNA was observed (19.8+/-19.0% decrease, P = 0.04, n = 7). In conclusion, the results of this study demonstrate that PAI-I expression is present in human isolated adipocytes and that it is enhanced in human adipose tissue in vitro by exogenous TNF-alpha. Furthermore our data support the possibility of a main role of endogenous TNF-alpha on human adipose tissue PAI-1 expression. This cytokine, produced by human adipose tissue and causing insulin resistance, may be a link in the clinical relationship between insulin-resistance syndrome and increased PAI-1 plasma levels.     

Outcome of patients with cirrhosis requiring intensive care unit support: Prospective assessment of predictors of mortality

Determinants of outcome and the utility of the Child-Pugh score and the acute physiology and chronic health evaluation (APACHE) II score as predictors of outcome were prospectively assessed in 54 consecutive patients with cirrhosis requiring intensive care unit (ICU) management. Overall mortality in the ICU was 43% (23/54). Child-Pugh scores did not differ between survivors or nonsurvivors (12.8 versus 12.3, P = 0.26), however APACHE II scores (P = 0.007), acute physiology scores (P = 0.006), and Karnofsky scores (P = 0.001) were significant predictors of outcome. By univariate analysis, requirement of mechanical ventilation analysis (P = 0.001), duration of mechanical ventilation (P = 0.001), pulmonary infiltrates (P = 0.0001), infections (P = 0.047), gastrointestinal bleeding (P = 0.005), and serum creatinine ≥1.5 mg/dl (P = 0.0005) were significantly associated with mortality. By logistic regression analysis only pulmonary infiltrates (P = 0.0001) and renal dysfunction (P = 0.041) were independent predictors of mortality. When controlled for the severity of illness (APACHE II scores), the mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Our study not only identified predictors of poor outcome in patients with cirrhosis requiring ICU care but also provided data that may have implications for optimal timing for transplantation. Received Feb. 2, 1997; accepted June 27, 1997     

Foot pad skin biopsy in mouse models of hereditary neuropathy

Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities--fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration-undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS.